The proposed research deals with the metabolism, or biotransformation, of the characteristic chemical constituents of Cannabis sativa L. by selected microorganisms, comprising both fungi and bacteria. A number of microbes are being examined for their ability to effect hydroxylations and other oxidative transformations of (-)-delta 9-tetrahydrocannabinol and other cannabinoids. Pure cannabinoids will be incubated with growing vegetative cultures, resting cell suspensions or spores of microorganisms which are suspected of being able to form hydroxylated or other polar metabolites characteristic of mammalian systems. Thin-layer chromatography and gas-liquid chromatography-mass spectroscopy will be used as analytical techniques in the assay for microorganisms capable of metabolizing cannabinoids and in the initial identification of polar metabolites. Particular attention will be given to determining whether the microorganisms examined produce known physiologically active or chemially interesting mammalian metabolites. The possibility of producing important cannabinoid metabolites by fermentation in large enough quantities to allow for pharmacological and toxicological testing will be investigated. Novel polar metabolites resulting from extensive modification of cannabinoids may provide clues to aspects of mammalian metabolism which are not yet fully understood.